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Rapid and longer-term antidepressant effects of repeated-dose intravenous ketamine for patients with unipolar and bipolar depression.

Wei Zheng, Yan-Ling Zhou, Wei-Jian Liu, Cheng-Yu Wang, Yan-Ni Zhan, Han-Qiu Li, Li-Jian Chen, Ming Ding Li, Yu-Ping Ning

Journal of Psychiatric Research November 2018 DOI: 10.1016/j.jpsychires.2018.09.013 (opens in new tab)

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AI-extracted from the abstract
Characteristics Observational cohort Peer reviewed
Sample size 97
Population Chinese patients with unipolar (n=77) and bipolar (n=20) depression
Intervention Ketamine
Dose 0.5 mg/kg over 40 min
Duration Six infusions, assessments up to 26 days
Measures Montgomery-Asberg Depression Rating Scale (MADRS), Scale for Suicidal Ideations (SSI)-part 1, 14-item Hamilton Anxiety Scale (HAMA), Brief Psychiatric Rating Scale (BPRS)-positive symptoms, Clinician Administered Dissociative States Scale (CADSS)
Topics Depression Ketamine Esketamine
Keywords Efficacy Response Tolerability
Key findings Six repeated ketamine infusions produced response in 68.0% and remission in 50.5% of patients with unipolar or bipolar depression, with rapid reductions in depression, suicidal ideation, and anxiety scores within four hours of the first infusion that were sustained across subsequent infusions. Response was associated with response at 24 hours after the first infusion, income of at least 4000 yuan per month, and no prior psychiatric hospitalization.

Abstract

Single-dose intravenous (IV) injection of ketamine has shown rapid but transient antidepressant effects. The strategy of repeated-dose ketamine infusions to maintain antidepressant effects has received little systematic study. This study was conducted to examine the efficacy and tolerability of six ketamine infusions in Chinese patients with unipolar and bipolar depression. Ninety seven patients with unipolar (n = 77) and bipolar (n = 20) depression received repeated ketamine infusions (0.5 mg/kg over 40 min) with continuous vital sign monitoring. Depressive symptoms were measured by the Montgomery-Asberg Depression Rating Scale (MADRS). Suicidal ideation was assessed using the Scale for Suicidal Ideations (SSI)-part 1. Anxiety symptoms were evaluated with the 14-item Hamilton Anxiety Scale (HAMA). Adverse psychopathological and dissociative effects were assessed using the Brief Psychiatric Rating Scale (BPRS)-positive symptoms and Clinician Administered Dissociative States Scale (CADSS), respectively. Patients were assessed at baseline, 4 and 24 h, and 3, 4, 5, 6, 8, 9, 10, 11, 12, 13 and 26 days. After six ketamine infusions, the response and remission rates were 68.0% and 50.5%, respectively. There were significant decreases in MADRS, SSI-part 1, and HAMA scores within four hours following the first ketamine infusion, and the decreases were sustained over the subsequent infusion period. The nonresponder subgroup manifested rapid significant improvement in suicidal ideations throughout the course of treatment. After the six ketamine infusions, the response was positively associated with the response at 24 h after the first infusion (OR = 8.94), personal income ≥4000 yuan/month (OR = 3.04), and no history of psychiatric hospitalization (OR = 3.41). Only CADSS scores had a mild but marginally significant increase after the first infusion but with a significant BPRS score decrease. Six ketamine infusions were safe and effective in patients with unipolar and bipolar depression. The rapid and robust antidepressant and antisuicidal effects of ketamine infusion within four hours were sustained following the subsequent infusions.

Comparable studies

Other observational and cohort studies on ketamine for depression, most cited first.

Study Year Design Participants
Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder 2012 Observational cohort n = 30
Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... 2017 Observational cohort n = 59
Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... 2014 Post hoc analysis of pooled data from four studies n = 108
An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder 2011 Observational cohort n = 14
Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... 2019 Observational cohort n = 25

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